This ongoing Program Project is focused on mechanisms of lung injury and the role of phagocytic cells and their products in the pathogenesis of acute and progressive (chronic) lung injury. The Program Project features investigators in three academic departments (Pathology, Pediatrics and Internal Medicine) and has been highly successful in terms of both individual projects as well as collaborative scientific ventures between projects. The renewal program features six projects and three cores. The projects include: I (Ward), Mediation of Immune Complex Injury; II (Kunkel), Granulomatous Lung Inflammation; III (Boxer), Neutrophil Activation in Acute Pulmonary Disease; IV (Phan), Macrophage Function in Lung Injury and Fibrosis; V (Ward), Adenine Nucleotide Effects on Leukocyte Activation and Oxygen Radical Formation; and VI (Killen), Molecular Biology of Injury to Alveolar Wall Cells. The Cores Include: A (Ward), Administrative; B (Kunkel), Molecular Biology and Immunology, C (Johnson), Morphology. The current Core D (Flow Cytometry) will be replaced by non- flow cytometric-based assays. The scientific focus of the next five years will be a definition of products of inflammatory cells (neutrophils, lymphocytes, macrophages, platelets) and inflammatory mediators (cytokines, oxygen radicals, eicosanoids, growth factors, etc.) and how these factors are involved in both acute and progressive lung injury. The established record of productivity and the demonstrated close collaborations between these groups of investigators provide the foundations for a continuing and successful Program Project.